DESCRIPTION: The application presents two focused specific aims related to establishing the role of Eph-like receptors and their associated ligands in the development and maintenance of the statoacoustic ganglion. The first is to identify the cell-type specific pattern of expression of Eph-like receptors and ligands in otocysts and the statoacoustic ganglion. The second is to test the ability of the Eph- like molecules to promote outgrowth or survival of the statoacoustic ganglion cells in culture. Eph-like molecules form the largest known family of receptor tyrosine kinases, and, based on their presence on cells and nerve fibers of the statoacoustic ganglion and on cells within the sensory epithelia of the otocysts, it has been hypothesized that they play a role in regulating nerve/hair cell interactions at very early stages of development. The experiments use in situ hybridization and Northern blotting experiments to localize and quantitate mRNA, and use immunoglobulin tagged Eph-like ligands and receptors to immunolocalize and quantitate proteins. Culture conditions will be used for assaying the effects of endogenously supplied Eph-like molecules. The experiments proposed in this application will form the groundwork for future studies on the inner ear under conditions where there are genetically or environmentally induced auditory and vestibular deficits.